Diagnosing HIV-Associated Neurocognitive Disorders (HAND) requires attributing neurocognitive impairment and functional decline at least partly to HIV-related brain effects. Depressive symptom severity, whether attributable to HIV or not, may influence self-reported functioning. We examined longitudinal relationships among objective global cognition, depressive symptom severity, and self-reported everyday functioning in people with HIV (PWH).

Longitudinal data from 894 PWH were collected at a university-based research center (2002–2016). Participants completed self-report measures of everyday functioning to assess both dependence in instrumental activities of daily living (IADL) and subjective cognitive difficulties at each visit, along with depressive symptom severity (BDI-II). Multilevel modeling examined within- and between-person predictors of self-reported everyday functioning outcomes.

Participants averaged 6 visits over 5 years. Multilevel regression showed a significant interaction between visit-specific global cognitive performance and mean depression symptom severity on likelihood of dependence in IADL (p = 0.04), such that within-person association between worse cognition and greater likelihood of IADL dependence was strongest among individuals with lower mean depressive symptom severity. In contrast, participants with higher mean depressive symptom severity had higher likelihoods of IADL dependence regardless of cognition. Multilevel modelling of subjective cognitive difficulties showed no significant interaction between global cognition and mean depressive symptom severity (p > 0.05).

The findings indicate a link between cognitive abilities and IADL dependence in PWH with low to moderate depressive symptoms. However, those with higher depressive symptoms severity report IADL dependence regardless of cognitive status. This is clinically significant because everyday functioning is measured through self-report rather than performance-based assessments.

Despite advances in antiretroviral treatment (ART), human immunodeficiency virus (HIV) can detrimentally affect everyday functioning. Neurocognitive impairment (NCI) and current depression are common in people with HIV (PWH) and can contribute to poor functional outcomes, but potential synergies between the two conditions are less understood. Thus, the present study aimed to compare the independent and combined effects of NCI and depression on everyday functioning in PWH. We predicted worse functional outcomes with comorbid NCI and depression than either condition alone.

PWH enrolled at the UCSD HIV Neurobehavioral Research Program were assessed for neuropsychological performance, depression severity (≤minimal, mild, moderate, or severe; Beck Depression Inventory-II), and self-reported everyday functioning.

Participants were 1,973 PWH (79% male; 66% racial/ethnic minority; Age: M = 48.6; Education: M = 13.0, 66% AIDS; 82% on ART; 42% with NCI; 35% BDI>13). ANCOVA models found effects of NCI and depression symptom severity on all functional outcomes (ps < .0001). With NCI and depression severity included in the same model, both remained significant (ps < .0001), although the effects of each were attenuated, and yielded better model fit parameters (i.e., lower AIC values) than models with only NCI or only depression.

Consistent with prior literature, NCI and depression had independent effects on everyday functioning in PWH. There was also evidence for combined effects of NCI and depression, such that their comorbidity had a greater impact on functioning than either alone. Our results have implications for informing future interventions to target common, comorbid NCI and depressed mood in PWH and thus reduce HIV-related health disparities.

Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

To cope with homonegativity-generated stress, gay, bisexual and other men who have sex with men (GBM) use more mental health services (MHS) compared with heterosexual men. Most previous research on MHS among GBM uses data from largely white HIV-negative samples. Using an intersectionality-based approach, we evaluated the concomitant impact of racialization and HIV stigma on MHS use among GBM, through the mediating role of perceived discrimination (PD).

We used baseline data from 2371 GBM enrolled in the Engage cohort study, collected between 2017 and 2019, in Montreal, Toronto and Vancouver, using respondent-driven sampling. The exposure was GBM groups: Group 1 (n = 1376): white HIV-negative; Group 2 (n = 327): white living with HIV; Group 3 (n = 577): racialized as non-white HIV-negative; Group 4 (n = 91): racialized as non-white living with HIV. The mediator was interpersonal PD scores measured using the Everyday Discrimination Scale (5-item version). The outcome was MHS use (yes/no) in the prior 6 months. We fit a three-way decomposition of causal mediation effects utilizing the imputation method for natural effect models. We obtained odds ratios (ORs) for pure direct effect (PDE, unmediated effect), pure indirect effect (PIE, mediated effect), mediated interaction effect (MIE, effect due to interaction between the exposure and mediator) and total effect (TE, overall effect). Analyses controlled for age, chronic mental health condition, Canadian citizenship, being cisgender and city of enrolment.

Mean PD scores were highest for racialized HIV-negative GBM (10.3, SD: 5.0) and lowest for white HIV-negative GBM (8.4, SD: 3.9). MHS use was highest in white GBM living with HIV (GBMHIV) (40.4%) and lowest in racialized HIV-negative GBM (26.9%). Compared with white HIV-negative GBM, white GBMHIV had higher TE (OR: 1.71; 95% CI: 1.27, 2.29) and PDE (OR: 1.68; 95% CI: 1.27, 2.24), and racialized HIV-negative GBM had higher PIE (OR: 1.09; 95% CI: 1.02, 1.17). Effects for racialized GBMHIV did not significantly differ from those of white HIV-negative GBM. MIEs across all groups were comparable.

Higher MHS use was observed among white GBMHIV compared with white HIV-negative GBM. PD positively mediated MHS use only among racialized HIV-negative GBM. MHS may need to take into account the intersecting impact of homonegativity, racism and HIV stigma on the mental health of GBM.

Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). The neuropathological hallmarks of aMCI/AD are amyloid-ß42 (Aß42) plaque and phosphorylated tau (p-tau) accumulation. Neurofilament light chain protein (NfL) is a marker of neuronal injury in AD and other neurodegenerative diseases. In this study, we assessed the prognostic value of the CSF AD pathology markers of lower Aß42, and higher p-tau, p-tau/Aß42 ratio, and NfL levels to identify an aMCI-like profile among older PWH and differentiating it from HAND. We assessed the relationship between aMCI and HAND diagnosis and AD biomarker levels

Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium (NNTC). CSF Aß42, Aß40, p-tau and NfL were measured by commercial immunoassay. Participants completed a neurocognitive evaluation assessing the domains of learning, recall, executive function, speed of information processing, working memory, verbal fluency, and motor. Memory domains were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, and aMCI was defined as impairment (<1.0 SD below normative mean) on two or more memory outcomes among HVLT-R and BVMT-R learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (<1.0 SD below normative mean) in 2 or more cognitive domains. A series of separate linear regression models were used to examine how the levels of CSF p-tau, Aß42, p-tau/Aß42 ratio, and NfL relate to aMCI and HAND status while controlling for demographic variables (age, gender, race and education). Covariates were excluded from the model if they did not reach statistical significance.

58% percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. PWH with aMCI had higher levels of CSF p-tau/Aß42 ratio compared to PWH without aMCI (ß=.222, SE=.001, p=.043) while controlling for age (ß=.363, p=.001). No other AD biomarker significantly differed by aMCI or HAND status.

Our results indicate that the CSF p-tau/Aß42 ratio relates specifically to an aMCI-like profile among PWH with high rates of cognitive impairment across multiple domains in this advanced HIV disease cohort. Thus, the p-tau/Aß42 ratio may have utility in disentangling aMCI from HAND and informing the need for further diagnostic procedures and intervention. Further research is needed to fully identify, among a broader group of PWH, who is at greatest risk for aMCI/AD and whether there is increased risk for aMCI/AD among PWH as compared to those without HIV.

Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.

283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.

Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).

PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

Workload is a useful construct in human factors and neuroergonomics research that describes “the perceived relationship between the amount of mental [and physical] processing capability or resources and the amount required by the task”. We apply this concept to neuropsychology and assess several dimensions of workload as it relates to performance on the Trail Making Test.

Twenty college students completed the Trail Making Test (TMT). After completion of each Part A and B, workload was assessed with the NASA-Task Load Index (NASA-TLX), a popular self-report measure of workload including subscales: Mental Demand, Physical Demand, Temporal Demand, Performance, Effort, and Frustration, with an overall average total score as well.

Completion time differed of course between Parts A and B (p < .001). Of more interest, overall workload differed between TMT A (M = 20.33, SD = 13.32) and TMT B (M = 35.79, SD = 17.37) (p < .001, h2 = .68). The greatest subscale differences were with Mental Demand (p < .001, h2 = .68) and Effort (p < .001, h2 = .59), but Physical Demand also showed a difference (p < .007, h2 = .33). Temporal Demand showed the smallest and nonsignificant difference (p = .081, h2 = .152).

Based on previous research in our lab, most results were expected and understandable. As we know with the TMT, Part B is more cognitively demanding (in various ways) than Part A. The greater Physical Demand with Part B is a somewhat more complex finding, needing a solid explanation. Finally, the NASA-TLX appears to be a valid instrument of workload with a standard neuropsychologist test. We argue it can provide useful interesting information in the assessment of cognitive status in clinical populations.

Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.

The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and

relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).

APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).

Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

Positive psychological attributes have been associated with better health outcomes and quality of life among people with HIV (PWH). Recently, we identified two latent factors (internal strengths, socioemotional support) among 7 positive psychological attributes through factor analysis (Ham et al., 2022). Depression was inversely associated with both factors. Our current aim was to investigate associations between these latent factors, neurocognition, and daily functioning among PWH.

106 PWH and 90 HIV- participants were included in cross-sectional analyses (Mage = 51.3, 77% men, 60% White). Seven positive psychological questionnaires, a neuropsychological battery covering 7 domains, two daily functioning questionnaires (Patient’s Assessment of Own Functioning (PAOFI); Independent Activities of Daily Living (IADL)), and a depression symptom questionnaire (Center for Epidemiologic Studies Depression Scale) were administered. Internal strengths and socioemotional support composite z-scores were calculated using HIV- participants’ scores as reference. Outcomes included global and domain-specific neurocognitive T-scores (demographically-adjusted), global deficit score (GDS), number of functional impairments (PAOFI), and number of functional declines (IADL). Main effects of HIV status, latent factors, and their interaction were included in linear (neurocognition) and Poisson (daily functioning) regressions. Significant interactions were followed up by simple effects analyses and nonsignificant interactions were removed. Depressive symptoms and demographics associated with daily functioning were included as covariates.

PWH exhibited worse neurocognitive performance (global, executive functioning, processing speed, learning, recall, GDS) and reported greater functional difficulties and depressive symptoms compared to HIV-counterparts (ps < 0.05). For neurocognition, there were socioemotional support x HIV status (B = 2.39, p = 0.04) and internal strengths x HIV status (B = 2.70, p < 0.05) interactions on verbal fluency, accounting for depressive symptoms, such that only PWH had a positive association between socioemotional support and verbal fluency (B = 1.97, p = 0.01). Removing nonsignificant interactions, there was a main effect of socioemotional support on global cognition (B = 1.01, p = 0.04) and psychomotor speed (B = 1.83, p = 0.02), independent of HIV status and depressive symptoms. For daily functioning, there was a socioemotional support x HIV status interaction on IADL declines (B = 0.42, p = 0.02), accounting for depressive symptoms and education, such that only HIV- participants had an inverse relationship between socioemotional support and IADL declines (B = -0.64, p < 0.001). Removing non-significant interactions, there were main effects of internal strengths on PAOFI impairments (B = -0.36, p < 0.001) and IADL declines (B = -0.38, p < 0.001), independent of HIV status and depressive symptoms.

Among PWH, both positive psychological factors were associated with better neurocognition, even after adjusting for depressive symptomatology. Though internal strengths were associated with better daily functioning regardless of HIV status, socioemotional support was not related to daily functioning in PWH. While mechanisms underlying these associations cannot be established cross-sectionally, it is possible that among people with medical illnesses complicated by cognitive disturbance, positive psychological factors relate to improved health-related behaviors (e.g., better disease management). Additionally, better neurocognition, including cognitive reserve, may engender greater resilience and improved ability to marshal social support.

This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long–term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression.

An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months.

Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23–2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01–2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01–1.09) and HR 1.06 (95% CI 1.01–1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78–0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81–1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse.

The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse.